Association between control group therapy and magnitude of clinical benefit of cancer drugs.
Authors: Consolacion Molto, Ariadna Tibau, Aida Bujosa, Jose Carlos Tapia, Abhenil Mittal, Faris Tamimi, Eitan Amir
Journal: Journal of Clinical Oncology (2022)

e18604 Background: Oncology societies have developed tools to quantify the magnitude of clinical benefit. These include the American Society of Clinical Oncology Value Framework (ASCO-VF) version 2, the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) version 1.1, the National Comprehensive Cancer Network (NCCN) Evidence Blocks and the ASCO Cancer Research Committee criteria (ASCO-CRC). Associations between the characteristics of approved drugs and magnitude of clinical benefit have been explored in depth. Here, we assess the association between characteristics of control group therapy and magnitude of clinical benefit. Methods: We searched Drugs@FDA to identify new solid tumor cancer drugs approved based on randomized trials (RCTs) between January 2012 and December 2021. Substantial clinical benefit was defined as: overall survival gain ≥ 2.5 months and progression-free survival gain ≥ 3 months for the ASCO-CRC (palliative setting only); ASCO-VF threshold score ≥45 (palliative and curative setting); NCCN Evidence Blocks threshold score ≥16 (palliative and curative setting); and grade A or B for trials of curative intent and 4 or 5 for those of non-curative intent using ESMO-MCBS. Associations between characteristics of control group therapy (e.g. type of active therapy, use of matched placebo and overlap between experimental and control therapy) and substantial clinical benefit scores were explored using logistic regression. Results: We identified 174 RCTs supporting the approval of 76 drugs for 164 indications. Of these, 47% (82/174) were placebo-controlled trials among which 42% (34/82) comprised active treatment with a matched placebo. Substantial clinical benefit was observed in 45%, 46%, 72% and 73% using the ESMO-MCBS, ASCO-VF, NCCN Evidence Blocks and ASCO-CRC, respectively. These low proportions resulted in an inability to fit multivariable models adequately. RCTs with a control group comprising of active treatment with a matched placebo were associated with significantly lower odds of substantial benefit with ESMO-MCBS (OR 0.27, P = .003) and ASCO-VF (OR 0.30, P = .008) but not with NCCN Evidence Blocks (OR 0.74, P = .55) or ASCO-CRC criteria (OR 1.36, P = .54). Similar results were observed when excluding trials in the curative setting. There was a non-significant association with higher odds of substantial benefit with ESMO-MCBS with trials in which the control group was chemotherapy (OR 1.97, P = .07). For ASCO-CRC a non-significant association in the opposite direction was observed (OR 0.40, P = .06). Conclusions: Clinical benefit scales can be sensitive to the type of control group therapy. RCTs with an active treatment and matched placebo in the control group were less likely to be scored as providing substantial clinical benefit using the ESMO-MCBS and the ASCO-VF scales. Control group therapy did not influence NCCN Evidence Blocks or ASCO-CRC scores.